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Glioblastoma is one of the most aggressive and difficult-to-treat brain cancers, with tumors often able to resist radiation and chemotherapy. Researchers at The Ohio State University Comprehensive Cancer Center have identified a protein called SET that could help explain how the cancer survives treatment and potentially provide a new way to make existing therapies more effective.
Rather than replacing current treatments, the approach aims to weaken glioblastoma cells so they become more vulnerable to therapies already used against the disease. In laboratory and animal experiments, blocking SET and related proteins reduced tumor formation and increased the sensitivity of surviving cancer cells to radiation.
The research focused on protein phosphatase 2A, or PP2A, an enzyme that helps regulate cellular processes involved in growth, survival and responses to treatment-related damage. The researchers found that glioblastoma cells can suppress PP2A through three proteins: ANP32A, CIP2A and SET.
When the scientists interfered with these proteins in laboratory and animal models, fewer cancer cells survived. The remaining cells were also more susceptible to radiation, suggesting that restoring PP2A activity could potentially undermine some of glioblastoma’s defenses.
“Glioblastoma is hard to treat because it can adapt and survive,” said Arnab Chakravarti, MD, chair of radiation oncology at the OSUCCC – James. He said the findings suggest that restoring PP2A activity could make tumor cells less capable of surviving treatment, potentially allowing radiation and chemotherapy to work more effectively.
The researchers are now investigating whether SET and other proteins that inhibit PP2A can be safely targeted with drugs. The team also examined an FDA-approved antipsychotic medication known to increase PP2A activity, providing another potential avenue for studying the pathway.
However, the researchers emphasized that the drug is not an approved treatment for glioblastoma and should not be used for that purpose outside a clinical trial.
The findings remain preliminary and have not been tested in human patients. Independent clinical studies will be needed to determine whether targeting SET or PP2A can actually improve outcomes for people with glioblastoma.
The study appeared in the May 2026 issue of Cancer Letters and received support from the National Institutes of Health, National Cancer Institute and The Ohio State University Comprehensive Cancer Center.
